THE EFFECT of BTK INHIBITION on PLATELET ACTIVATION by GPVI and CLEC-2 by Phillip Lindsay Ross Nicolson

Total Page:16

File Type:pdf, Size:1020Kb

THE EFFECT of BTK INHIBITION on PLATELET ACTIVATION by GPVI and CLEC-2 by Phillip Lindsay Ross Nicolson THE EFFECT OF BTK INHIBITION ON PLATELET ACTIVATION BY GPVI AND CLEC-2 by Phillip Lindsay Ross Nicolson A thesis submitted to the University of Birmingham for the degree of DOCTOR OF PHILOSOPHY Institute of Cardiovascular Sciences College of Medical and Dental Sciences University of Birmingham October 2018 University of Birmingham Research Archive e-theses repository This unpublished thesis/dissertation is copyright of the author and/or third parties. The intellectual property rights of the author or third parties in respect of this work are as defined by The Copyright Designs and Patents Act 1988 or as modified by any successor legislation. Any use made of information contained in this thesis/dissertation must be in accordance with that legislation and must be properly acknowledged. Further distribution or reproduction in any format is prohibited without the permission of the copyright holder. Abstract Background The novel Btk inhibitor ibrutinib has recently been introduced into the clinic for treatment of lymphoproliferative disorders (LPDs) where it is unexpectedly associated with major bleeding. It has been shown to block GPVI and CLEC-2- mediated platelet function with the former correlating with bleeding. This contrasts with patients who are deficient in GPVI or Btk who experience minor/no bleeding respectively. Mice that lack CLEC-2 also have no bleeding diathesis but are protected from thromboinflammation. Aims This study aims to investigate the discrepancy between the bleeding seen with ibrutinib and those that lack Btk. It also aims to examine whether ibrutinib can block CLEC-2 signalling in mouse and human venous thrombosis. Results Ibrutinib blocks GPVI signalling due to off-target effects which occur because of the high clinical doses that are used. It blocks CLEC-2 signalling at ~50-fold lower concentrations and reduces venous thrombosis rates in patients taking it for LPD. Conclusions Lowering the dose of ibrutinib or developing a more specific Btk inhibitor would ameliorate the major bleeding that is seen with ibrutinib. Btk inhibitors are suitable for further study as inhibitors of CLEC-2 signalling in human venous thrombosis. Publications arising from this thesis Manuscripts • Nicolson PLR, Hughes CE, Watson S, Nock SH, Hardy AT, Watson CN, Montague SJ, Malcor JD, Thomas MR, Tomlinson MG, Pratt G, Watson SP. Inhibition Of Btk By Btk-Specific Concentrations Of Ibrutinib And Acalabrutinib Delays But Does Not Block Platelet Aggregation To GPVI. Haematologica. 2018;103(12):2097-2108 DOI: 10.3324/haematol.2018.193391 Book Chapter • Haining EJ, Nicolson PLR, Onselaer MB, Poulter NS, Thomas MR, Rayes J and Watson SP. (2019). ‘GPVI and CLEC-2’ in Michelson AD (ed.) Platelets, 4th edition. Elsevier/Academic Press, pp 213-226. Dedication I would like to dedicate this thesis to my wife Pippa and my children William and Emily without whom I would not have achieved the spiritual, physical and psychological nourishment necessary to sustain me throughout this degree. Acknowledgements This work was supported by the University of Birmingham Institute of Cardiovascular Sciences and the Institute of Translational Medicine as well as the British Heart Foundation through the clinical research training fellowship (FS/17/20/32738). I would particularly like to acknowledge Lorraine Harper for enabling me to get on the first rung of the ladder to start this work. First and foremost for help in almost every aspect of laboratory work I want to thank the incredible Stef Watson without whom numerous experiments would have failed due to lack of expertise and reagents. Practical help with other aspects of laboratory work was received from Craig Hughes and Alex Hardy for the aggregation and biochemical assays; from Alex Bye and Jon Gibbins for the 2+ Ca mobilisation assay; from Vicky Simms and Steve Thomas for the flow adhesion assays; from Abs Khan, Natalie Poulter, Jeremy Pike and Dee Kavanagh for the spreading and super-resolution microscopy assays and Lizzie Haining, Julie Rayes and Alex Brill as well as all the staff at the Biomedical Services Unit for the animal work. Social and gastronomic support in the lab was obtained through close collaboration with Abs Khan, Natalie Poulter, Chris Smith and Pushpa Patel. For help with collection and provision of patient blood I would like to thank Mark Crowther, Nick Pemberton, Salim Shafeek, Kate Arthur, Gaynor Pemberton, Lesley Candlin and Rebekah Hart at Worcestershire Royal Hospital, Shankara Paneesha, Aarnoud Huissoon, Hayley Clifford, Alison Hardy and Melanie Kelly at Birmingham Heartlands Hospital and Guy Pratt, Tina McSkeane, Gillian Marshall and Michelle Harry at the Queen Elizabeth Hospital. For help with collection of human blood and tissue and collaboration on the same I would also like to thank Rachel Brown from the Queen Elizabeth Hospital, Jane Steele and Gareth Bicknell from the Human Biomaterials Resource Centre and John Welsh and Mark Kahn from the University of Pennsylvania in Philadelphia. I would also like to thank Andrew Wilkinson and Robert Neely from the School of Chemistry at the University of Birmingham for their help with the chemical analysis of ibrutinib and acalabrutinib. For working so diligently under my supervision and providing work to go towards the conclusions of this thesis (even if not directly examinable) I want to thank Josh Hinds. In particular for help with statistical analysis for fellowship applications and work included in this thesis I would like to thank Peter Nightingale from the Queen Elizabeth Hospital for so willingly giving up his time for me. I would also like to thank Gill Lowe, Guy Pratt, Gayle Halford and Mike Tomlinson for helping me learn to cope with Steve Watson. The gratitude for this also extends to every other member of the Birmingham Platelet Group. Outside the lab I would like to thank my parents and parents-in-law for their ongoing support with childcare to enable conference travel and unsociable working hours. I would also like to thank my good friends Ian Butler and Parag Gajendragadkar for forcing me out on my bike to the Clent hills and Italian Dolomites respectively. I would like to thank Iain Johnston, Alessandro Di Maio, Matt MacKenzie and Abs Khan for similarly dragging me out to music rehearsal studios in Digbeth. I would also like to thank Dave Grohl, Nate Mendel, Taylor Hawkins and Chris Shiflett as well as Shawn Crahan, Craig Jones, Mick Thomson, Corey Taylor, Sid Wilson, Chris Fehn, Jim Root, Alessandro Venturella, Jay Weinberg, Joey Jordison, Paul Gray and Donnie Steele for fuelling the thesis writing process. Finally I would like to thank my supervisors, Steve Watson and Guy Pratt, for their unfailing support before and throughout this work. For many practical, financial and psychological reasons, without Steve, none of what follows would have been possible. I also want to thank him for bringing me down a peg or two at the times when my confidence outweighed my abilities; “Pip, in science, you never prove anything”. Table of Contents CHAPTER 1: GENERAL INTRODUCTION ................................................................................. 1 1.1 Introduction to platelets ........................................................................................................ 1 1.1.1 Platelet production ........................................................................................................ 1 1.1.2 Platelet structure ........................................................................................................... 2 1.1.3 Platelet function ............................................................................................................. 3 1.1.3.1 The role of platelets in haemostasis and thrombosis ................................................. 3 1.1.3.2 Functions of platelets outside haemostasis ............................................................... 5 1.1.4 Major platelet receptors and ligands ............................................................................. 6 1.1.4.1 GPCRs ....................................................................................................................... 7 1.1.4.2 ITAM receptors ........................................................................................................... 8 1.1.4.3 Adhesion receptors .................................................................................................. 10 1.2 Haemostasis ...................................................................................................................... 11 1.2.1 Classical Haemostasis ................................................................................................ 11 1.2.2 Inflammatory haemostasis .......................................................................................... 13 1.3 Platelets in thrombosis and thromboinflammation ............................................................. 14 1.3.1 Arterial thrombosis ...................................................................................................... 14 1.3.2 Venous thrombosis ..................................................................................................... 15 1.3.3 Immunothrombosis and thromboinflammation ............................................................ 18 1.3.4 ITAM receptors as new targets in thrombosis and thromboinflammation ................... 19 1.4 Bruton’s tyrosine kinase (Btk) and its inhibitors ................................................................. 21 1.4.1 Btk ..............................................................................................................................
Recommended publications
  • Slipknot Apresenta a Turnê "Prepare for Hell" Em São Paulo, Em Setembro
    Slipknot apresenta a turnê "Prepare for Hell" em São Paulo, em setembro Famosos por seu som pesado e por seu figurino característico que inclui macacões e máscaras, banda anuncia show no dia 27 de setembro, na Arena Anhembi. Ingressos à venda no site da Livepass. Um dos maiores fenômenos internacionais do heavy metal, o Slipknot traz para o país a turnê “Prepare for Hell", que tem base em seu quinto e mais recente álbum de estúdio, .5: The Gray Chapter, lançado em 2014. A apresentação única em São Paulo acontece no dia 27 de setembro, na Arena Anhembi, dentro da plataforma Samsung Galaxy S6 Live Music Rocks. A banda promete um ambicioso show de rock pesado acompanhado por músicas que mostram o futuro doSlipknot, sem esquecer das raízes da banda, tudo isso em um novo palco, especialmente criado para a turnê de 2015. O grupo se apresenta ainda no Rock in Rio, no dia 25 de setembro. A apresentação de São Paulo contará com a participação especial da banda Mastodon. Apresentados por Samsung Galaxy S6 e com patrocínio da Sky e Budweiser, os shows são uma realização da Move Concerts e fazem parte da nova plataforma de música Samsung Galaxy S6 Live Music Rocks. Mais informações sobre venda de ingressos, abaixo, em “Serviço”. Famosos pelo figurino de seus shows, que inclui macacões e máscaras criados especialmente para a banda, o Slipknot promete apresentar no show de São Paulo um set list que reúne não só seus maioreshits, como “Wait and Bleed”, “Duality” e “Psychosocial”, mas também músicas do novo álbum: “The Devil in I”, “Custer” e “The Negative One”.
    [Show full text]
  • Download Day of the Gusano Mp4 SLIPKNOT "Day of the Gusano" 01
    download day of the gusano mp4 SLIPKNOT "Day Of The Gusano" 01. Sarcastrophe 02. Eeyore 03. Custer 04. (sic) 05. Me Inside 06. Psychosocial 07. Duality 08. Before I Forget 09. The Devil In I 10. Vermillion 11. Prosthetics 12. Metabolic / 742617000027 13. Spit It Out 14. The Heretic Anthem 15. Wait And Bleed 16. Surfacing / Til We Die. RATING: 7/10. It takes mucho cojones—18 of them, apparently—to stage a giant, carnival-like festival for your first live appearance in a foreign country, and that's exactly what SLIPKNOT did in December of 2015 when they held the seventh Knotfest in Toluca, Mexico (about an hour's drive west of Mexico City). The band's performance was captured on the just-released "Day Of The Gusano" , but instead of being advertised as a live DVD or concert film, "Gusano" (Spanish for "maggot", a word long ago appropriated by the band to describe its fans) has been described as a "documentary". Don't be misled, however, for around four-fifths of its 90-minute running time, "Gusano" , which was screened in select theaters around the world, shows SLIPKNOT performing a 16-song set before an enormous, passionate crowd. (For reasons unknown, the DVD and Blu-ray editions rearrange the track listing from the audio-only release. That version showcases the group's complete 17-song set in the same order in which it was performed, and omits "People = Shit" .) The remaining quarter-hour or so primarily features snippets of interviews with unmasked band members and a handful of unidentified Mexican fans, with both camps attempting to portray the group's arrival in town as a Really.
    [Show full text]
  • Slipknot – Iowa (2001)
    Slipknot – Iowa (2001) Album named after the band's home state of Iowa Bio of the band: Slipknot is a heavy-metal band consisting of nine members, all of whom are male, who became popular because of its extreme music and dramatic stage performances. This group was first formed in the late 1995 in the unlikely locale of Des Moines, IA. It had 3 percussionists, 2 guitarists, 1 bassist, a DJ, a sampler and a lead singer. Aside from their real names, members of the band are also referred to by numbers 0 through 8 and each of them also wears a mask, which they said is part of their personality, like an extension of their body. To explain that, all the group members believe that wearing the masks shows more of what they are like inside and what the music does to them inside. Members include: #1 Joey Jordon- drums (1995-2013) # 2 Paul Gray- bass (1995-2010) #3 Chris Fehn- percussion (1998– present) #4 Jim Root – guitar (1999 – present) #5 Craig Jones - samples (1996 – present) #6 Shawn Crahan -percussion (1995 – present) #7 Mick Thompson -guitar (1996 – present) #8 Corey Taylor - vocals (1997 – present) #9 Sid Wilson - DJ (1998 – present) Iowa Biography: The state of Iowa is probably best known as "the middle of nowhere." Most non-residents consider it the corn-and-pig-state, a geographical black hole. After a couple years of relentless touring in support of their self-titled breakthrough album, Slipknot regrouped to record Iowa, an ode to their home state that consolidates and punctuates everything that had garnered the band its cultish following.
    [Show full text]
  • Iowa State Daily, May 2010 Iowa State Daily, 2010
    Iowa State Daily, May 2010 Iowa State Daily, 2010 5-25-2010 Iowa State Daily (May 25, 2010) Iowa State Daily Follow this and additional works at: http://lib.dr.iastate.edu/iowastatedaily_2010-05 Part of the Higher Education Commons, and the Journalism Studies Commons Recommended Citation Iowa State Daily, "Iowa State Daily (May 25, 2010)" (2010). Iowa State Daily, May 2010. 3. http://lib.dr.iastate.edu/iowastatedaily_2010-05/3 This Book is brought to you for free and open access by the Iowa State Daily, 2010 at Iowa State University Digital Repository. It has been accepted for inclusion in Iowa State Daily, May 2010 by an authorized administrator of Iowa State University Digital Repository. For more information, please contact [email protected]. 1 TUESDAY May 25, 2010, Volume 205 >> Number 3 >> 40 cents >> iowastatedaily.com >> An independent newspaper serving Iowa State since 1890 Swimming against the odds Special Olympian Ben Schnable strives to overcome the current in the sport he loves Conservation Station Your eating directory Burritos on Welch Traveling, learning platform Looking for a new place to dine Fighting Burrito is moving 3 teaches Ames children at? Check AmesEats.com 4 to Welch Avenue 2 PAGE 2 | Iowa State Daily | Tuesday, May 25, 2010 A look at Iowa State The information in the log comes from the ISU and the City of Ames police departments’ Only at iowastatedaily.com Police Blotter : ISU, Ames Police Departments records. All those accused of violating the law are innocent until proven guilty in a court of law. at 10:20 a.m.) (reported at 3:21 p.m.) possession of alcohol under May Full coverage of Benjamin Yeager, 7304 Rachel Winterbottom re- the legal age.
    [Show full text]
  • Co W „34” Piszczy? Julia Marek, 5A Wielka Orkiestra Świątecznej Pomocy
    MIESIĘCZNIK SZKOŁY PODSTAWOWEJ NR 34 im. WOJSKA POLSKIEGO w Poznaniu na osiedlu Bolesława Śmiałego 107 Nr 3 ( 196 ) grudzień/styczeń 2020 Marzę, aby ludzie więcej robili dla własnego zdrowia – rozmowa z panią Agnieszką Wielgosik, szkolną Detektyw pielęgniarką. Piórko zanotował „Szkolniaczek”: Co robi szkolna pielęgniarka? Agnieszka Wielgosik: Główną rolą pielęgniarki szkolnej jest Ósmoklasiści zmagali wykonywanie działań profilaktycznych mających za zadanie zapobieganie i wczesne wykrywanie chorób (np. badania bilansowe, się z egzaminem próbnym. badania przesiewowe, nadzorowane szczotkowanie zębów preparatem fluorkowym ), promocja zdrowia, a w niej edukacja Okazaliśmy jak zwykle zdrowotna oraz udzielanie pomocy medycznej w urazach i nagłych dużo serca, włączając zachorowaniach. się w akcje charytatywne. „Szk.”: Czy praca w szkole jest trudna? Lubi Pani swoją pracę? Kiermasz świąteczny A.W.: Pielęgniarka szkolna w całości sama odpowiada za świadczone i wspólne kolędowanie usługi, ich jakość, terminy realizacji, współpracę z personelem wprowadziły nas w placówki, opiekunami uczniów, instytucjami pozaszkolnymi oraz świąteczny nastrój. udzielaną pomoc medyczną, co wymaga stałego doszkalania na A po świętach wielu płaszczyznach. najtrudniejszy czas dla Lubię swojąCo pracę w i„34” z przyjemnością piszczy codziennie? przychodzę do uczniów i nauczycieli – gabinetu w Zespole Szkolno -Przedszkolnym nr 8. wystawianie ocen. Po raz kolejny „34” zagrała razem z Wielką Orkiestrą Świątecznej Pomocy. Już wkrótce ferie zimowe! 1 „Szk.”: Z jakimi dolegliwościami przychodzą najczęściej uczniowie do gabinetu? A.W.: Do szkolnego gabinetu przychodzą uczniowie z bardzo różnymi dolegliwościami, więc indywidualnie podchodzę do każdego przypadku. Najczęściej udaje się udzielić porady w gabinecie szkolnym, ale zdarzają się sytuacje, gdy potrzebna jest interwencja pogotowia ratunkowego. „Szk.”: Gdzie jeszcze może pracować pielęgniarka? A.W.: Każda pielęgniarka może również pracować w placówkach medycznych (np.
    [Show full text]
  • The Discursive Construction of Ideal Heavy Metal
    1 Vulgar Discourses of Power: The Discursive Construction of Ideal Heavy Metal Subjectivity and the Erasure of Black, Indigenous, and Women of Colour in Heavy Metal Music Culture By Michelle Bona A Thesis Submitted to Saint Mary’s University, Halifax, Nova Scotia in Partial Fulfillment of the Requirements for the Degree of Master of Arts in Women and Gender Studies April 2021, Halifax, Nova Scotia Copyright Michelle Bona, 2021 Approved: Dr. Tatjana Takševa Supervisor Approved: Dr. Jacqueline Warwick Examiner Approved: Dr. Tracy Moniz Reader Date: 23 April 2021 2 Abstract Vulgar Discourses of Power: The Discursive Construction of Ideal Heavy Metal Subjectivity and the Erasure of Black, Indigenous, and Women of Colour in Heavy Metal Music Culture By Michelle Bona Heavy metal music culture has been a bastion of working-class white masculinity since its beginnings in the early 1970s. Through canonization and Historical documentation, white male dominance has been ensured, obscuring contributions made by white female performers and erasing black, Indigenous, and women of colour (BIWoC) from the genre. Utilizing feminist critical discourse analysis (feminist CDA) to examine texts by canonized male bands reveals the discursive parameters of ideal heavy metal subjectivity (IHMS). Exploration of texts created by white female performers, including a case study of Arch Enemy vocalist Alissa White-Gluz, isolates the necessity for white female performers to reproduce the discourses of IHMS in order to secure their participation in the culture, further contributing to the erasure of BIWoC performers. However, feminist CDA also reveals transformative potential within these texts to de-centre IHMS as the default subject position and shows white women’s agency and resiliency as performers.
    [Show full text]
  • Testfunda General Knowledge Quizzes
    TestFunda General Knowledge Quizzes Book 1 The LEADER in Online Test Prep Table of Contents Online Quiz #01 (02-Sep-08) .................................................. 3 Online Quiz #02 (12-Sep-08) .................................................. 6 Online Quiz #03 (26-Sep-08) .................................................. 8 Online Quiz #05 (14-Oct-08) ................................................. 11 Online Quiz #07 (24-Oct-08) ................................................. 15 Online Quiz #10 (20-Nov-08) ............................................... 24 Online Quiz #12 (05-Dec-08) ................................................ 27 Online Quiz #14 (19-Dec-08) ................................................ 37 Online Quiz #16 (02-Jan-09) ................................................. 39 Online Quiz #18 (16-Jan-09) ................................................. 49 Online Quiz #20 (30-Jan-09) ................................................. 55 Online Quiz #22 (13-Feb-09) ................................................ 60 Online Quiz #24 (27-Feb-09) ................................................ 66 Online Quiz #26 (13-Mar-09) ............................................... 71 Online Quiz #28 (27-Mar-09) ............................................... 76 Online Quiz #30 (10-Apr-09) ................................................ 80 Online Quiz #32 (24-Apr-09) ................................................ 85 Online Quiz #34 (08-May-09) ............................................... 91 Online Quiz #36 (22-May-09)
    [Show full text]
  • Visualisasi Lagu-Lagu Band Slipknot
    VISUALISASI LAGU-LAGU BAND SLIPKNOT JURNAL PENCIPTAAN KARYA SENI Diajukan Oleh: BAYU DEMAS NIM 1212322021 PROGAM STUDI SENI RUPA MURNI JURUSAN SENI MURNI FAKULTAS SENI RUPA INSTITUT SENI INDONESIA YOGYAKARTA 2019 UPT Perpustakaan ISI Yogyakarta Jurnal Tugas Akhir Penciptaan Karya Seni berjudul: VISUALISASI LAGU-LAGU BAND SLIPKNOT diajukan oleh Bayu Demas, NIM 1212322021, Program Studi Seni Grafis, Jurusan Seni Murni, Fakultas Seni Rupa Institut Seni Indonesia Yogyakarta, telah dipertanggungjawabkan di depan Tim Penguji Tugas Akhir pada tanggal 8 Juli 2019 dan dinyatakan telah memenuhi syarat untuk diterima. Ketua Jurusan Seni Murni/ Progam Studi/ Ketua/ Anggota Lutse Lambert Daniel Morin, M. Sn NIP 19761007 200604 1 001 UPT Perpustakaan ISI Yogyakarta A. Judul Visualisasi Lagu-Lagu Band Slipknot B. Abstrak Oleh: Bayu Demas 1212322021 ABSTRAK Setiap individu manusia memiliki banyak hal yang menemani dan menginspirasi perjalanan kehidupan mereka. Bagi pribadi penulis hal ini adalah seni, yang salah satunya adalah seni musik. Mendengarkan musik Metal, terutama dari grup band Slipknot, dapat dijadikan sebagai media untuk melampiaskan perasaan-perasaan yang tidak dapat diungkapkan seperti kekesalan, kemarahan, dan kekecewaan. Dengan tema- tema yang terkandung dalam lagu-lagu band Slipknot, dirasakan adanya hubungan dengan sebagian perjalanan kehidupan penulis. Lagu-lagu ini kemudian divisualkan dalam bentuk visualisasi yang menceritakan isi, dan tema dari lagu-lagu tersebut sebagai bentuk apresiasi terhadap band ini. Visualisasi lagu-lagu ini menggunakan pendekatan visual yang ilustratif dengan harapan dapat membantu penikmat karya untuk lebih memahami tema atau cerita yang terkandung di dalam lagu-lagu Slipknot yang telah menemani dan menginspirasi kehidupan penulis. Kata Kunci: Visualisasi, Lagu, Slipknot, Musik, Metal. UPT Perpustakaan ISI Yogyakarta ABSTRACT Each and every individual have things that had them accompanied and inspired by through their life.
    [Show full text]
  • Los Rolling Stones
    10/07/2012 20:47 Cuerpo E Pagina 4 Cyan Magenta Amarillo Negro 4 MIÉRCOLES 11 DE JULIO DE 2012 TÍMPANO TRADICIÓN Y VERDAD SERÁ EN LA ESCALA MADRE Unafuentecercanaalacantanteha Slipknot publica su primer álbum revelado que Adele y Simon, su no- recopilatorio vio, querían mantener la feliz noticia Los estadounidenses Slipknot, una de las últimas grandes en secreto mientras fuera posible. marcas mundiales del rock “metalero” en su variante más co- “Adele apenas ha salido a la calle en rrosiva y esquizoide, publicarán el 24 de julio Antennas To los últimos meses, así ha podido Hell , el primer disco recopilatorio de su carrera.Ese trabajo, mantener el secreto. Dejó de actuar que recorrerá más de 20 años de trayectoria de esta banda de hace unos meses, y desde entonces Iowa, se editará en dos formatos, según ha precisado hoy War- se ha dedicado al futuro bebé por ner Music. Por un lado, se lanzará un disco sencillo y, por completo”, contó la fuente a la re- otro, un álbum doble con un DVD que contendrá su actuación vista Heat.Varios amigos han en el festival Download en 2009. apuntado que Simon, que ya tiene Nacido en los años 90, el grupo sufrió en 2010 la importan- una niña de una relación anterior, te pérdida de uno de sus fundadores y principal compositor, y la cantante han querido tener un el bajista Paul Gray. Actualmente está formado por el voca- hijo desde que empezaron su no- lista Corey Taylor, los guitarras Mick Thomson y Jim Root, agencias viazgo el año pasado.
    [Show full text]
  • Creator of New NAIT Confessions Page Speaks, P. 16
    THE NUGGET IS TAKING A WEEK OFF FOR MIDTERMS – NEXT ISSUE NOV. 5! THE Thursday, October 22, 2015 Volume 53, Issue 8 NAIT YOUR STUDENT NEWSPAPERNUGGET FOR MORE THAN 50 YEARS, EDMONTON, ALBERTA, CANADA TBH CONFESSES Creator of new NAIT confessions page speaks, p. 16 Graphic design by Connor O’Donovan 2 The Nugget Thursday, October 22, 2015 NEWS&FEATURES Hoping for more space It’s not just food services or technol- ogy areas that are feeling the pinch. Wan- der down the E Hallway and you can see many students crammed into the small study areas offset in the adjoining halls. Some students resort to lining the hall- ways, sitting on the floor to study or snack between classes. Have a group project to complete? There are precious few loca- tions on campus where you can gather NICOLAS BROWN quietly to collaborate, mostly limited to Issues Editor the new Teaching and Learning Commons @bruchev on the north-end of campus. We can just Space, just like time, appears to be a ignore the limited space available for stu- finite resource on campus at NAIT. Stu- dents to organize social activities, since dents everywhere are feeling the squeeze that could take an entire article in itself, and it might not be getting better any time but NAITSA’s limited office space is soon. indicative of that issue. As NAIT’s enrolment continues to Certainly, NAIT’s continued expan- grow, it feels like we’re finding less and sion, with the addition of the new HET less space on campus. Trying to access a building and the planned opening of the mikeroeconomics.blogspot.com computer workstation at the HP Centre CAT Building in Fall 2016, will have vacated space? No doubt more programs between classes doesn’t mean more space.
    [Show full text]
  • Slipknot We Are Not Your Kind Release Date
    Slipknot We Are Not Your Kind Release Date Civil Mack regives, his vapour drove invocating ethically. Absonant and cubic Pascal propagandizing her epitaph interglacial tot and pinnacled treacherously. Limiting Penn always dispatch his chimps if Winny is dipped or gambolling soberly. Solange knowles has been different synth modules and are we are you may take on maternity leave much to make the complicated yet On the superpowers in barcelona, nor play this new wave of those quicksilver hooks just such as inaccurate as this. Although every slipknot we not your kind? Slipknot are not your email to hurt me? Problems playing through many facets and not increase the song but. Wanyk is released one produced by your email address to? Going through the record arrived on their fallen bassist alessandro futurella on the sonic aesthetic, linkin park and south. Go to your kind of slipknot are headbanging to pick up their other releases music first released an account with every month, and rejuvenated album? Very difficult for your kind of we are. Jack lawrence and unpredictable and then they going to not view their promotional posts by the band releases music in barcelona, the litigation is. Palm muting creates one more friends explore your entire cannes film custom block document from that. Neither jaffe nor slipknot we not? Between police officers at the bedridden kardashian attend the time off a very common when they did. You give visitors an acting and its first five weeks of played around seemingly impossible corners, from a much color, according to experiment every subgenre and old style.
    [Show full text]
  • LAMPIRAN.Pdf
    Hak cipta dan penggunaan kembali: Lisensi ini mengizinkan setiap orang untuk menggubah, memperbaiki, dan membuat ciptaan turunan bukan untuk kepentingan komersial, selama anda mencantumkan nama penulis dan melisensikan ciptaan turunan dengan syarat yang serupa dengan ciptaan asli. Copyright and reuse: This license lets you remix, tweak, and build upon work non-commercially, as long as you credit the origin creator and license it on your new creations under the identical terms. Team project ©2017 Dony Pratidana S. Hum | Bima Agus Setyawan S. IIP LAMPIRAN Proses kerja reporter..., Timotius Manggala Prasetia, FIKOM UMN, 2015 Jl. Krisan 1 Sektor I.5 Blok F4 No 19 TIMOTIUS MANGGALA Bumi Serpong Damai – Tangerang 15321 Phone : 081574462497 PRASETIA E-mail: [email protected] C U R R I C U L U M V I T A E Data Pribadi Nama Lengkap : Timotius Manggala Prasetia Nama Panggilan : Timothy Tempat/Tanggal Lahir : Jakarta, 8 Juni 1993 Jenis Kelamin : Laki-laki Status : Single Warga Negara : Indonesia Pendidikan Sekolah Tempat Tahun Sekolah Dasar : Santa Ursula, Bumi Serpong Damai 1999-2005 Sekolah Menengah : Homeschooling Paket B 2007-2008 Pertama Sekolah Menengah Akhir : Homeschooling Paket C 2008-2010 Kuliah : Jurusan Jurnalistik, Fakultas Ilmu 2010-Sekarang Komunikasi, Universitas Multimedia Nusantara Indeks Prestasi : 3,03 Pengalaman Organisasi Nama Organisasi Spesifikasi Tahun Anggota Pameran Commpres Divisi Artistik 2013 (Communication Press) tahun 2013, Universitas Multimedia Nusantara Pengalaman Kerja Perusahaan Deskripsi Tahun Deuszine
    [Show full text]